Coating solutions comprising segmented reactive block copolymers

ABSTRACT

This invention is directed toward surface treatment of a device. The surface treatment comprises the attachment of reactive segmented block copolymers to the surface of the substrate by means of reactive functionalities of the terminal functionalized surfactant material reacting with complementary surface reactive functionalities in monomeric units along the polymer substrate. The present invention is also directed to a surface modified medical device, examples of which include contact lenses, intraocular lenses, vascular stents, phakic intraocular lenses, aphakic intraocular lenses, corneal implants, catheters, implants, and the like, comprising a surface made by such a method.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of Provisional Patent Application No. 61/016,844 filed Dec. 27, 2007; Provisional Patent Application No. 61/016,845 filed Dec. 27, 2007; Provisional Patent Application No. 61/016,841 filed Dec. 27, 2007; and Provisional Patent Application No. 61/016,843 filed Dec. 27, 2007.

FIELD OF INVENTION

This invention relates to coating solutions comprising a new class of tailored polymers useful as surface coatings for ophthalmic devices. These polymers can be specifically tailored using controlled radical polymerization processes and contain a number of functional domains. Controlled radical polymerization allows the facile synthesis of segmented block copolymers with tunable chemical composition that, as a result, show different chemical properties than those prepared via conventional free radical polymerization. Segmented block copolymers with substrate binding domain(s) containing functional groups (glycidyl groups, activated esters, amino groups, hydroxyl groups, carboxylic acid groups, etc.) and hydrophilic domain(s) show good surface properties when covalently bound to substrates containing complimentary functionality.

BACKGROUND OF THE INVENTION

Medical devices such as ophthalmic lenses are made from a wide variety of materials. In the contact lens field materials are broadly categorized into conventional hydrogels or silicone hydrogels. Recently, the use of silicone-containing materials (silicone hydrogels) has been preferred. These materials can vary greatly in water content. However, regardless of their water content, silicone materials tend to be relatively hydrophobic, non-wettable, and have a high affinity for lipids. Methods to modify the surface of silicone devices by increasing their hydrophilicity and improving their biocompatibility are of great importance.

A number of copolymers for surface coatings have been investigated. U.S. Pat. No. 6,958,169 discloses providing a medical device formed from a monomer mixture comprising a hydrophilic device-forming monomer including a copolymerizable group and an electron donating moiety, and a second device-forming monomer including a copolymerizable group and a reactive functional group; and, contacting a surface of the medical device with a wetting agent including a proton donating moiety reactive with the functional group provided by the second lens-forming monomer and that complexes with the electron donating moiety provided by the hydrophilic lens-forming monomer.

U.S. Pat. No. 6,858,310 discloses a method of modifying the surface of a medical device to increase its biocompatibility or hydrophilicity by coating the device with a removable hydrophilic polymer by means of reaction between reactive functionalities on the hydrophilic polymer with functionalities that are complementary on or near the surface of the medical device.

U.S. Pat. No. 6,599,559 discloses a method of modifying the surface of a medical device to increase its biocompatibility or hydrophilicity by coating the device with a removable hydrophilic polymer by means of reaction between reactive functionalities on the hydrophilic polymer which functionalities are complementary to reactive functionalities on or near the surface of the medical device.

U.S. Pat. No. 6,428,839 discloses a method for improving the wettability of a medical device, comprising the steps of: (a) providing a medical device formed from a monomer mixture comprising a hydrophilic monomer and a silicone-containing monomer, wherein said medical device has not been subjected to a surface oxidation treatment; (b) contacting a surface of the medical device with a solution comprising a proton-donating wetting agent, whereby the wetting agent forms a complex with the hydrophilic monomer on the surface of the medical device in the absence of a surface oxidation treatment step and without the addition of a coupling agent.

Many copolymers are currently made using conventional free radical polymerization techniques with the structure of the polymer being completely random or controlled by the reactivity ratios of the respective monomers. By using controlled free radical polymerization techniques one is able to assemble copolymers in a controlled fashion and, in turn, they show completely different solution and coating properties than copolymers prepared using conventional free radical polymerization techniques. Controlled free radical polymerization can be conducted by a variety of methods, such as ATRP (atom transfer radical polymerization) and RAFT (Reversible addition-fragmentation chain transfer polymerization).

SUMMARY

In accordance with the present disclosure, the invention relates generally to coating solutions comprising reactive segmented block copolymers for forming bound coatings in the manufacture of medical devices. As used herein the terms “bound”, “binding”, or terms of similar import, refer to covalent linkages between the reactive segmented block copolymer and the surface functionality of the device which results in the association of a coating composition with the device. Examples of suitable devices include contact lenses, intraocular lenses, intraocular lens inserters, vascular stents, phakic intraocular lenses, aphakic intraocular lenses, corneal implants, catheters, implants, and the like.

Reactive segmented block copolymers prepared through Atom Transfer Radical Polymerization (“ATRP”) methods in accordance with the invention herein may have the following generic formula (I): R₁−[(A)_(m)]_(p)−[(B)_(n)]_(q)−X  (I) wherein R₁ is the reactive residue of a moiety capable of acting as an initiator for Atom Transfer Radical Polymerization, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and X is a halogen capping group of the initiator for Atom Transfer Radical Polymerization. It should be noted, that there are many processes for the post polymerization removal or transformation of the halogen capping group of an initiator for Atom Transfer Radical Polymerization which are known to one of ordinary skill in the art. Therefore polymers prepared using ATRP according to the invention herein would include those where X is a halogen capping group of the initiator for Atom Transfer Radical Polymerization and those polymers that have undergone post polymerization removal or transformation of the halogen capping group of an initiator for Atom Transfer Radical Polymerization (i.e., derivatized reaction product). The polymers which contain halogen end-groups can be utilized in a host of traditional alkyl halide organic reactions. In one example, the addition of tributyltin hydride to the polymeric alkyl halide in the presence of a radical source (AIBN, or Cu(I) complex) leads to a saturated hydrogen-terminated polymer. In another example, by replacing tributyltin hydride with allyl tri-n-butylstannane, polymers with allyl end groups can be prepared. The terminal halogen can also be displaced by nucleophilic substitution, free-radical chemistry, or electrophilic addition catalyzed by Lewis acids to yield a wide variety of telechelic derivatives, such as alkenes, alkynes, alcohols, thiols, alkanes, azides, amines, phosphoniums, or epoxy groups, to mention a few.

Reactive segmented block copolymers prepared through Reversible addition-fragmentation chain transfer polymerization (“RAFT”) methods in accordance with the invention herein may have the following generic formula (II): R₁−[(A)_(m)]_(p)−[(B)_(n)]_(q)−R₂  (II) wherein R₁ is a radical forming residue of a RAFT agent or free radical initiator, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and R₂ is a thio carbonyl thio fragment of the chain transfer agent. RAFT agents based upon thio carbonyl thio chemistry are well known to those of ordinary skill in the art and would include, for example, xanthates, trithiocarbonates and dithio esters. It should be noted, that there are many processes for the post polymerization removal or transformation of the thio carbonyl thio fragment of the chain transfer agent which are known to one of ordinary skill in the art. Therefore polymers prepared using RAFT agent according to the invention herein would include those where R₂ is a thio carbonyl thio fragment of the chain transfer agent and those polymers that have undergone post polymerization removal or transformation of the thio carbonyl thio fragment of the chain transfer agent (i.e., a derivatized reaction product). One example of such a transformation is the use of free radical reducing agents to replace the thio carbonyl thio group with hydrogen. Others include thermolysis of the end group or conversion of the thio carbonyl thio groups to thiol groups by aminolysis. A wide variety of telechelic derivatives can be prepared, such as alkenes, alkynes, alcohols, thiols, alkanes, azides, amines, phosphoniums, or epoxy groups, to mention a few.

Reactive segmented block copolymers prepared through reversible addition-fragmentation chain transfer polymerization (“RAFT”) methods in accordance with the invention herein may have the following generic formula (III): R1−[(B)n]q−[(A)m]p−R2−[(A)m]p−[(B)n]−R1  (III) wherein R1 is a radical forming residue of a RAFT agent or free radical initiator, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and R2 is a thio carbonyl thio group.

For each of the polymers of generic formula I, II and III the order of the block units is not critical and the reactive segmented block copolymer can contain more than two blocks. Therefore the reactive segmented block copolymers can be multiblock copolymers and include repetition of one or more blocks. As examples please see the nonlimiting representations below, each of which is intended to fall within generic formula I, II and III: −(A)_(m)−(B)_(n)−  (1) −(B)_(n)−(A)_(m)−  (2) −(A)_(m)−(B)_(n)−(A)_(m)−  (3)

Reactive segmented block copolymers useful in the invention herein may also contain blocks that would not be considered to be binding or hydrophilic, for example, polystyrene or polymethyl methacrylate. The presence of non binding or non hydrophilic block(s) within a polymer is contemplated as being within the scope of the claimed reactive segmented block copolymers and formulae I, II and III of the invention herein.

Provided herein is a method of forming a surface modified medical device, the method comprising providing a medical device having at least one group providing reactive functionality on at least one surface of the medical device; providing a surface modifying agent comprising a reactive segmented block copolymer comprising a hydrophilic block and a chemical binding unit block having reactivity that is complimentary to the at least one group providing surface functionality of the medical device; contacting the at least one surface having reactive functionality of the medical device with the surface modifying agent, and; subjecting the device surface and surface modifying agent to reaction conditions suitable for forming a covalent bond between the device surface and the surface modifying agent to form a surface modified medical device.

Also provided herein is a surface modified medical device comprising a medical device having at least one group providing reactive functionality on at least one surface of the medical device; and a reactive segmented block copolymer comprising a chemical binding unit block and a hydrophilic block applied to the surface of the medical device; whereby a chemical reaction between the surface functionality of the medical device and the one or more reactive segmented block copolymer comprising a chemical binding unit block and a hydrophilic block forms covalent bonds there between.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic example of atom-transfer radical polymerization (ATRP) used to make a segmented block copolymer in which there is an oligomeric block of the chemical binding unit at one end of the polymer followed by a large hydrophilic block;

FIG. 2 is the structural formula of various monomers which may be used to provide the reactive functionality of the segmented block copolymers of the invention herein;

FIG. 3 is a reaction schematic showing how RAFT polymerization can be used to polymerize block copolymers with functional domains.

DETAILED DESCRIPTION

The present invention relates generally to coating solutions comprising reactive segmented block copolymers. Compositions comprising the reactive segmented block copolymers are useful in providing surface bound coatings in the manufacture of medical devices. In preferred embodiments, the present invention relates to reactive segmented block copolymers having reactive functionality that is complimentary to surface functionality of a medical device such as an ophthalmic lens. It should be understood that the term “surface” is not to be limited to meaning “at least one complete surface”. Surface coverage does not have to be even or complete to be effective for surface functionality or surface treatment. The reactive segmented block copolymers of the present invention are useful as coatings for biocompatible materials including both soft and rigid materials commonly used for ophthalmic lenses, including contact lenses.

Reactive segmented block copolymers prepared through Atom Transfer Radical Polymerization (“ATRP”) methods in accordance with the invention herein may have the following generic formula (I): R₁−[(A)_(m)]_(p)−[(B)_(n)]_(q)−X  (I) wherein R₁ is the reactive residue of a moiety capable of acting as an initiator for Atom Transfer Radical Polymerization, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and X is a halogen capping group of the initiator for Atom Transfer Radical Polymerization. It should be noted, that there are many processes for the post polymerization removal or transformation of the halogen capping group of an initiator for Atom Transfer Radical Polymerization which are known to one of ordinary skill in the art. Therefore polymers prepared using ATRP according to the invention herein would include those where X is a halogen capping group of the initiator for Atom Transfer Radical Polymerization and those polymers that have undergone post polymerization removal or transformation of the halogen capping group of an initiator for Atom Transfer Radical Polymerization (i.e., derivatized reaction product). The polymers which contain halogen end-groups can be utilized in a host of traditional alkyl halide organic reactions. In one example, the addition of tributyltin hydride to the polymeric alkyl halide in the presence of a radical source (AIBN, or Cu(I) complex) leads to a saturated hydrogen-terminated polymer. In another example, by replacing tributyltin hydride with allyl tri-n-butylstannane, polymers with allyl end groups can be prepared. The terminal halogen can also be displaced by nucleophilic substitution, free-radical chemistry, or electrophilic addition catalyzed by Lewis acids to yield a wide variety of telechelic derivatives, such as alkenes, alkynes, alcohols, thiols, alkanes, azides, amines, phosphoniums, or epoxy groups, to mention a few.

Reactive segmented block copolymers prepared through Reversible addition-fragmentation chain transfer polymerization (“RAFT”) methods in accordance with the invention herein may have the following generic formula (II): R₁−[(A)_(m)]_(p)−[(B)_(n)]_(q)−R₂  (II) wherein R₁ is a radical forming residue of a RAFT agent or free radical initiator, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and R₂ is a thio carbonyl thio fragment of the chain transfer agent. RAFT agents based upon thio carbonyl thio chemistry are well known to those of ordinary skill in the art and would include, for example, xanthates, trithiocarbonates and dithio esters. It should be noted, that there are many processes for the post polymerization removal or transformation of the thio carbonyl thio fragment of the chain transfer agent which are known to one of ordinary skill in the art. Therefore polymers prepared using RAFT agent according to the invention herein would include those where R₂ is a thio carbonyl thio fragment of the chain transfer agent and those polymers that have undergone post polymerization removal or transformation of the thio carbonyl thio fragment of the chain transfer agent (i.e., a derivatized reaction product). One example of such a transformation is the use of free radical reducing agents to replace the thio carbonyl thio group with hydrogen. Others include thermolysis of the end group or conversion of the thio carbonyl thio groups to thiol groups by aminolysis. A wide variety of telechelic derivatives can be prepared, such as alkenes, alkynes, alcohols, thiols, alkanes, azides, amines, phosphoniums, or epoxy groups, to mention a few.

Reactive segmented block copolymers prepared through reversible addition-fragmentation chain transfer polymerization (“RAFT”) methods in accordance with the invention herein may have the following generic formula (III): R1−[(B)n]q−[(A)m]p−R2−[(A)m]p−[(B)n]q−R1  (III) wherein R1 is a radical forming residue of a RAFT agent or free radical initiator, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and R2 is a thio carbonyl thio group.

For each of the polymers of generic formula I, II and III the order of the block units is not critical and the reactive segmented block copolymer can contain more than two blocks. Therefore the reactive segmented block copolymers can be multiblock copolymers and include repetition of one or more blocks. As examples please see the nonlimiting representations below, each of which is intended to fall within generic formula I, II and III: −(A)_(m)−(B)_(n)−  (1) −(B)_(n)−(A)_(m)−  (2) −(A)_(m)−(B)_(n)−(A)_(m)−  (3)

Reactive segmented block copolymers useful in the invention herein may also contain blocks that would not be considered to be binding or hydrophilic, for example, polystyrene or polymethyl methacrylate. The presence of non binding or non hydrophilic block(s) within a polymer is contemplated as being within the scope of the claimed reactive segmented block copolymers and formulae I, II and III of the invention herein.

The present invention provides materials useful for surface modifying contact lenses and like medical devices through the use of complementary functionality. Although only contact lenses will be referred to hereinafter for purposes of simplicity, such reference is not intended to be limiting since the subject copolymers are suitable for surface modification of other medical devices such as phakic and aphakic intraocular lenses and corneal implants as well as contact lenses. Surface groups of the polymeric materials of the contact lenses and other biomedical devices are used to form chemical linkages, i.e., binding, with the reactive segmented block copolymers of the invention herein. The preferred reactive segmented block copolymers in the present invention are selected based on the specific surface groups of the polymeric material to be coated. In accordance with the present invention, the one or more reactive segmented block copolymers selected for surface modification should have complementary reactive chemical functionality to that of the surface groups of the substrate. Such complementary reactive chemical functionality enables a chemical reaction between the reactive segmented block copolymers and the complementary surface groups of the substrate to form covalent linkages there between. The one or more reactive segmented block copolymers are thus bound to the surface of the contact lens or like medical device to achieve surface modification thereof.

The reactive segmented block copolymer comprises a chemical binding unit block to provide the desired surface binding of the molecule. The chemical binding unit block can be varied and is determined based upon the intended use of the reactive segmented block copolymers. That is, the chemical binding unit block of the reactive segmented block copolymers is selected to provide functionality that is complementary with the surface functionality of the device.

Selection of the chemical binding unit monomer of the block copolymer is determined by the functional groups on the surface of the device. For example, if the reactive molecule on the surface of the device contains a carboxylic acid group, a glycidyl group containing monomer can be a chemical binding unit monomer of the reactive segmented block copolymer. If the reactive molecule on the surface of the device contains hydroxy or amino functionality, an isocyanate group or carbonyl chloride group containing monomers can be a chemical binding unit monomer of the reactive segmented block copolymer. A wide variety of suitable combinations of functional group containing monomers of the chemical binding unit complementary to reactive groups on the surface of the device will be apparent to those of ordinary skill in the art. For example, the chemical binding unit block may comprise a moiety selected from amine, hydroxyl, hydrazine, hydrazide, thiol (nucleophilic groups), carboxylic acid, carboxylic ester, including imide ester, orthoester, carbonate, isocyanate, isothiocyanate, aldehyde, ketone, thione, alkenyl, acrylate, methacrylate, acrylamide, sulfone, maleimide, disulfide, iodo, epoxy, sulfonate, thiosulfonate, silane, alkoxysilane, halosilane, and phosphoramidate. More specific examples of these groups include succinimidyl ester or carbonate, imidazolyl ester or carbonate, benzotriazole ester or carbonate, p-nitrophenyl carbonate, vinyl sulfone, chloroethylsulfone, vinylpyridine, pyridyl disulfide, iodoacetamide, glyoxal, dione, mesylate, tosylate, and tresylate. Also included are other activated carboxylic acid derivatives, as well as hydrates or protected derivatives of any of the above moieties (e.g. aldehyde hydrate, hemiacetal, acetal, ketone hydrate, hemiketal, ketal, thioketal, thioacetal). Preferred electrophilic groups include succinimidyl carbonate, succinimidyl ester, maleimide, benzotriazole carbonate, glycidyl ether, imidazoyl ester, p-nitrophenyl carbonate, acrylate, tresylate, aldehyde, and orthopyridyl disulfide. Examples of complementary functionality are provided below in Table 1.

TABLE 1 MONOMER/RESIDUE HAVING A COMPLEMENTARY REACTIVE REACTIVE FUNCTIONAL GROUP SURFACE FUNCTIONALITY Carboxylic acid, isocyanate, epoxy, Alcohol, amine, thiol, epoxy anhydride, lactone, lactam, oxazolone, maleimide, anhydride, acrylates,

Amine, thiol, alcohol,  

Carboxylic acid, isocyanate, epoxy, anhydride, lactone, lactam, oxazolone, maleimide, anhydride, acrylates

The chemical binding unit block of the reactive segmented block copolymers is oligomeric or polymeric and is sized to provide suitable binding to the surface of the medical device to be coated. Therefore the variable m of formula I, II or III can be between 1 and about 1000, preferably between 1 and about 100, most preferably between 1 and about 30.

In addition to the chemical binding unit, the reactive segmented block copolymers of the invention herein will also contain hydrophilic domain(s) showing good surface properties when the block copolymer is covalently bound to substrates containing complimentary functionality. The hydrophilic domain(s) will comprise at least one hydrophilic monomer, such as, HEMA, glyceryl methacrylate, methacrylic acid (“MAA”), acrylic acid (“AA”), methacrylamide, acrylamide, N,N′-dimethylmethacrylamide, or N,N′-dimethylacrylamide; copolymers thereof; hydrophilic prepolymers, such as ethylenically unsaturated poly(alkylene oxide)s, cyclic lactams such as N-vinyl-2-pyrrolidone (“NVP”), or derivatives thereof. Still further examples are the hydrophilic vinyl carbonate or vinyl carbamate monomers. Hydrophilic monomers can be nonionic monomers, such as 2-hydroxyethyl methacrylate (“HEMA”), 2-hydroxyethyl acrylate (“HEA”), 2-(2-ethoxyethoxy)ethyl(meth)acrylate, glyceryl(meth)acrylate, poly(ethylene glycol(meth)acrylate), tetrahydrofurfuryl(meth)acrylate, (meth)acrylamide, N,N′-dimethylmethacrylamide, N,N′-dimethylacrylamide(“DMA”), N-vinyl-2-pyrrolidone (or other N-vinyl lactams), N-vinyl acetamide, and combinations thereof. Still further examples of hydrophilic monomers are the vinyl carbonate and vinyl carbamate monomers disclosed in U.S. Pat. No. 5,070,215, and the hydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,910,277. The contents of these patents are incorporated herein by reference. The hydrophilic monomer also can be an anionic monomer, such as 2-methacryloyloxyethylsulfonate salts. Substituted anionic hydrophilic monomers, such as from acrylic and methacrylic acid, can also be utilized wherein the substituted group can be removed by a facile chemical process. Non-limiting examples of such substituted anionic hydrophilic monomers include trimethylsilyl esters of (meth)acrylic acid, which are hydrolyzed to regenerate an anionic carboxyl group. The hydrophilic monomer also can be a cationic monomer selected from the group consisting of 3-methacrylamidopropyl-N,N,N-trimethyammonium salts, 2-methacryloyloxyethyl-N,N,N-trimethylammonium salts, and amine-containing monomers, such as 3-methacrylamidopropyl-N,N-dimethyl amine. Other suitable hydrophilic monomers will be apparent to one skilled in the art.

The hydrophilic monomer block will be sized to provide the desirable surface coating property of the reactive segmented block copolymer. The size of the hydrophilic oligomeric or polymeric block may vary depending upon the substrate to be coated and the intended use. Therefore the variable n of formula I, II or III can be between I and about 10000, preferably between about 10 and about 1000, and more preferably between about 20 and about 300.

Atom-transfer radical polymerization (ATRP) can be used to prepare segmented block copolymers in which the molecular weight of each of the blocks and the entire polymer can be precisely controlled. As shown in FIG. 1, atom-transfer radical polymerization (ATRP) can be used to make a segmented block copolymer in which there is a block of the chemical binding unit at one end of the polymer followed by a large hydrophilic block. It should be understood that the order of addition of the monomer comprising the chemical binding unit domain and the monomer comprising the hydrophilic domain is not critical. A large number of monomers are available for the assembly of polymers (For example, see FIG. 2). Reversible addition-fragmentation chain transfer polymerization (RAFT) can also be used to prepare segmented block copolymers in which the molecular weight of each of the blocks and the entire polymer can be precisely controlled (see FIG. 3).

The reactive segmented block copolymers of the invention herein are useful in providing coatings for substrates. Examples of substrate materials useful with the present invention are taught in U.S. Pat. No. 5,908,906 to Künzler et al.; U.S. Pat. No. 5,714,557 to Künzler et al.; U.S. Pat. No. 5,710,302 to Künzler et al.; U.S. Pat. No. 5,708,094 to Lai et al.; U.S. Pat. No. 5,616,757 to Bambury et al.; U.S. Pat. No. 5,610,252 to Bambury et al.; U.S. Pat. No. 5,512,205 to Lai; U.S. Pat. No. 5,449,729 to Lai; U.S. Pat. No. 5,387,662 to Künzler et al.; U.S. Pat. No. 5,310,779 to Lai and U.S. Pat. No. 6,891,010 to Künzler et al.; which patents are incorporated by reference as if set forth at length herein.

The present invention contemplates the use of reactive segmented block copolymers with medical devices including both “hard” and “soft” contact lenses. As disclosed above, the invention is applicable to a wide variety of materials. Hydrogels in general are a well-known class of materials that comprise hydrated, cross-linked polymeric systems containing water in an equilibrium state. Silicon containing hydrogels generally have water content greater than about 5 weight percent and more commonly between about 10 to about 80 weight percent. Such materials are usually prepared by polymerizing a mixture containing at least one silicon containing monomer and at least one hydrophilic monomer. Typically, either the silicon containing monomer or the hydrophilic monomer functions as a crosslinking agent (a crosslinker being defined as a monomer having multiple polymerizable functionalities) or a separate crosslinker may be employed. Applicable silicon containing monomeric units for use in the formation of silicon containing hydrogels are well known in the art and numerous examples are provided in U.S. Pat. Nos. 4,136,250; 4,153,641; 4,740,533; 5,034,461; 5,070,215; 5,260,000; 5,310,779; and 5,358,995.

Examples of applicable silicon-containing monomeric units include bulky polysiloxanylalkyl(meth)acrylic monomers. An example of bulky polysiloxanylalkyl(meth)acrylic monomers are represented by the following Formula IV:

wherein:

-   X denotes —O— or —NR—; -   each R₁ independently denotes hydrogen or methyl; -   each R₂ independently denotes a lower alkyl radical, phenyl radical     or a group represented by

wherein each R′_(2′) independently denotes a lower alkyl or phenyl radical; and h is 1 to 10. Some preferred bulky monomers are methacryloxypropyl tris(trimethyl-siloxy)silane or tris(trimethylsiloxy)silylpropyl methacrylate, sometimes referred to as TRIS.

Another class of representative silicon-containing monomers includes silicon containing vinyl carbonate or vinyl carbamate monomers such as: 1,3-bis[4-vinyloxycarbonyloxy)butyl]tetramethyl-disiloxane; 3-(trimethylsilyl)propyl vinyl carbonate; 3-(vinyloxycarbonylthio)propyl-[tris(trimethylsifoxy)silane]; 3-[tris(tri-methylsiloxy)silyl]propyl vinyl carbamate; 3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate; 3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate; t-butyldimethylsiloxyethyl vinyl carbonate; trimethylsilylethyl vinyl carbonate; and trimethylsilylmethyl vinyl carbonate.

An example of silicon-containing vinyl carbonate or vinyl carbamate monomers are represented by Formula V:

-   -   wherein:         -   Y′ denotes —O—, —S— or —NH—;         -   R^(Si) denotes a silicon containing organic radical;         -   R₃ denotes hydrogen or methyl;         -   d is 1, 2, 3 or 4; and q is 0 or 1.         -   Suitable silicon containing organic radicals R^(Si) include             the following:             —(CH₂)_(n′)Si[(CH₂)_(m′)CH₃]₃;             —(CH₂)_(n′)Si[OSi(CH₂)_(m′)CH₃]₃;

-   -   and

-   -   wherein:         -   R₄ denotes

wherein p′ is 1 to 6;

-   -   -   R₅ denotes an alkyl radical or a fluoroalkyl radical having             1 to 6 carbon atoms;         -   e is 1 to 200; n′ is 1, 2, 3 or 4; and m′ is 0, 1, 2, 3, 4             or 5.

An example of a particular species within Formula V is represented by Formula VI.

Another class of silicon-containing monomers includes polyurethane-polysiloxane macromonomers (also sometimes referred to as prepolymers), which may have hard-soft-hard blocks like traditional urethane elastomers. They may be end-capped with a hydrophilic monomer such as HEMA. Examples of such silicon containing urethanes are disclosed in a variety of publications, including Lai, Yu-Chin, “The Role of Bulky Polysiloxanylalkyl Methacrylates in Polyurethane-Polysiloxane Hydrogels,” Journal of Applied Polymer Science, Vol. 60, 1193-1199 (1996). PCT Published Application No. WO 96/31792 discloses examples of such monomers, which disclosure is hereby incorporated by reference in its entirety. Further examples of silicon containing urethane monomers are represented by Formulae VII and VIII: E(*D*A*D*G)_(a)*D*A*D*E′; or  (VII) E(*D*G*D*A)_(a)*D*G*D*E′;  (VIII)

-   -   wherein:         -   D denotes an alkyl diradical, an alkyl cycloalkyl diradical,             a cycloalkyl diradical, an aryl diradical or an alkylaryl             diradical having 6 to 30 carbon atoms;         -   G denotes an alkyl diradical, a cycloalkyl diradical, an             alkyl cycloalkyl diradical, an aryl diradical or an             alkylaryl diradical having 1 to 40 carbon atoms and which             may contain ether, thio or amine linkages in the main chain;         -   * denotes a urethane or ureido linkage;         -   a is at least 1;         -   A denotes a divalent polymeric radical of Formula IX:

-   -   wherein:         -   each R_(s) independently denotes an alkyl or             fluoro-substituted alkyl group having 1 to 10 carbon atoms             which may contain ether linkages between carbon atoms;         -   m′ is at least 1; and         -   p is a number which provides a moiety weight of 400 to             10,000;         -   each of E and E′ independently denotes a polymerizable             unsaturated organic radical represented by Formula X:

-   -   wherein:         -   R₆ is hydrogen or methyl;         -   R₇ is hydrogen, an alkyl radical having 1 to 6 carbon atoms,             or a —CO—Y—R₉ radical wherein Y is —O—, —S— or —NH—;         -   R₈ is a divalent alkylene radical having 1 to 10 carbon             atoms;         -   R₉ is a alkyl radical having 1 to 12 carbon atoms;         -   X denotes —CO— or —OCO—;         -   Z denotes —O— or —NH—;         -   Ar denotes an aromatic radical having 6 to 30 carbon atoms;         -   w is 0 to 6; x is 0 or 1; y is 0 or 1; and z is 0 or 1.

A more specific example of a silicon containing urethane monomer is represented by Formula (XI):

wherein m is at least 1 and is preferably 3 or 4, a is at least 1 and preferably is 1, p is a number which provides a moiety weight of 400 to 10,000 and is preferably at least 30,

-   -   R₁₀ is a diradical of a diisocyanate after removal of the         isocyanate group, such as the diradical of isophorone         diisocyanate, and each E″ is a group represented by:

A preferred silicon containing hydrogel material comprises (in the bulk monomer mixture that is copolymerized) 5 to 50 percent, preferably 10 to 25 percent, by weight of one or more silicon containing macromonomers, 5 to 75 percent, preferably 30 to 60 percent, by weight of one or more polysiloxanylalkyl(meth)acrylic monomers, and 10 to 50 percent, preferably 20 to 40 percent, by weight of a hydrophilic monomer. In general, the silicon containing macromonomer is a poly(organosiloxane) capped with an unsaturated group at two or more ends of the molecule. In addition to the end groups in the above structural formulas, U.S. Pat. No. 4,153,641 to Deichert et al. discloses additional unsaturated groups, including acryloxy or methacryloxy. Fumarate-containing materials such as those taught in U.S. Pat. Nos. 5,512,205; 5,449,729; and 5,310,779 to Lai are also useful substrates in accordance with the invention. Preferably, the silane macromonomer is a silicon-containing vinyl carbonate or vinyl carbamate or a polyurethane-polysiloxane having one or more hard-soft-hard blocks and end-capped with a hydrophilic monomer.

Suitable hydrophilic monomers form hydrogels, such as silicon-containing hydrogel materials useful in the present invention. Examples of useful monomers include amides such as dimethylacrylamide, dimethylmethacrylamide, cyclic lactams such as n-vinyl-2-pyrrolidone and poly(alkene glycols) functionalized with polymerizable groups. Examples of useful functionalized poly(alkene glycols) include poly(diethylene glycols) of varying chain length containing monomethacrylate or dimethacrylate end caps. In a preferred embodiment, the poly(alkene glycol)polymer contains at least two alkene glycol monomeric units. Still further examples are the hydrophilic vinyl carbonate or vinyl carbamate monomers disclosed in U.S. Pat. No. 5,070,215, and the hydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,910,277. Other suitable hydrophilic monomers will be apparent to one skilled in the art.

Device Forming Additives and Comonomers

The monomer mix may, further as necessary and within limits not to impair the purpose and effect of the present invention, comprise various additives such as antioxidant, coloring agent, ultraviolet absorber and lubricant.

The monomer mix may be prepared by using, according to the end-use and the like of the resulting shaped polymer articles, one or at least two of the above comonomers and oligomers and, when occasions demand, one or more crosslinking agents.

Where the shaped polymer articles are for example medical products, in particular a contact lens, the monomer mix is suitably prepared from one or more of the silicon compounds, e.g. siloxanyl(meth)acrylate, siloxanyl(meth)acrylamide and silicon containing oligomers, to obtain contact lenses with high oxygen permeability.

The monomer mix may include additional constituents such as crosslinking agents, internal wetting agents, hydrophilic monomeric units, toughening agents, and other constituents as is well known in the art.

Although not required, the monomer mix may include toughening agents, preferably in quantities of less than about 80 weight percent e.g. from about 5 to about 80 weight percent, and more typically from about 20 to about 60 weight percent. Examples of suitable toughening agents are described in U.S. Pat. No. 4,327,203. These agents include cycloalkyl acrylates or methacrylates, such as: methyl acrylate and methacrylate, t-butylcyclohexyl methacrylate, isopropylcyclopentyl acrylate, t-pentylcycloheptyl methacrylate, t-butylcyclohexyl acrylate, isohexylcyclopentyl acrylate and methylisopentyl cyclooctyl acrylate. Additional examples of suitable toughening agents are described in U.S. Pat. No. 4,355,147. This reference describes polycyclic acrylates or methacrylates such as: isobornyl acrylate and methacrylate, dicyclopentadienyl acrylate and methacrylate, adamantyl acrylate and methacrylate, and isopinocamphyl acrylate and methacrylate. Further examples of toughening agents are provided in U.S. Pat. No. 5,270,418. This reference describes branched alkyl hydroxyl cycloalkyl acrylates, methacrylates, acrylamides and methacrylamides. Representative examples include: 4-t-butyl-2-hydroxycyclohexyl methacrylate (TBE); 4-t-butyl-2-hydroxycyclopentyl methacrylate; methacryloxyamino-4-t-butyl-2-hydroxycyclohexane; 6-isopentyl-3-hydroxycyclohexyl methacrylate; and methacryloxyamino-2-isohexyl-5-hydroxycyclopentane.

In particular regard to contact lenses, the fluorination of certain monomers used in the formation of silicon containing hydrogels has been indicated to reduce the accumulation of deposits on contact lenses made therefrom, as described in U.S. Pat. Nos. 4,954,587, 5,079,319, 5,010,141 and 6,891,010. Moreover, the use of silicon containing monomers having certain fluorinated side groups, i.e. —(CF₂)—H, have been found to improve compatibility between the hydrophilic and silicon containing monomeric units, as described in U.S. Pat. Nos. 5,387,662 and 5,321,108.

As stated above, surface structure and composition determine many of the physical properties and ultimate uses of solid materials. Characteristics such as wetting, friction, and adhesion or lubricity are largely influenced by surface characteristics. The alteration of surface characteristics is of special significance in biotechnical applications where biocompatibility is of particular concern. Thus, it is desired to provide a silicon containing hydrogel contact lens with an optically clear, hydrophilic surface film that will not only exhibit improved wettability, but which will generally allow the use of a silicon containing hydrogel contact lens in the human eye for extended period of time. In the case of a silicon containing hydrogel lens for extended wear, it would be further desirable to provide an improved silicon-containing hydrogel contact lens with an optically clear surface film that will not only exhibit improved lipid and microbial behavior, but which will generally allow the use of a silicon-containing hydrogel contact lens in the human eye for an extended period of time. Such a surface treated lens would be comfortable to wear in actual use and allow for the extended wear of the lens without irritation or other adverse effects to the cornea.

It would also be desirable to apply these surface enhancing coatings to implantable medical devices such as intraocular lens materials to reduce the attachment of lens epithelial cells to the implanted device and to reduce friction as the intraocular lens passes through an inserter into the eye. It would also be desirable to apply these surface enhancing coatings to intraocular lens inserters.

The present invention is useful for surface treatment of a polymeric device. The surface treatment comprises the binding of reactive segmented block copolymers to the surface of a polymeric medical device substrate by reacting complementary reactive functionalities of the reactive segmented block copolymers with reactive functionalities along the polymeric substrate surface.

As set forth above, for surface modification of contact lenses in accordance with the segmented block copolymers of the present invention, complementary functionality is incorporated between the surface of the contact lens material (i.e., the substrate) and the chemical binding unit block of the reactive segmented block copolymer used as a surface modification treatment polymer (surface modifying agent). For example, if a surface modifying agent has epoxide functionality, then the contact lens material to be treated must have a residue with complementary functionality that will react with that of the surface modifying agent. In such a case, the contact lens material could include a reactive prepolymer such as bis-α,ω-fumaryl butyl polydimethyl siloxane diacid to react with the surface modifying agent epoxide functionality. Likewise, if a contact lens is formed from material having a residue providing epoxide functionality, a surface modifying agent containing a 2-hydroxyethyl methacrylate functionality could be used for surface modification in accordance with the present invention. Such complementary chemical functionality enables binding to occur between the surface of the contact lens and the reactive groups of the one or more surface modifying agent's. This binding between functional groups forms covalent linkages there between. For example, a contact lens containing prepolymer having surface hydroxyl functional groups preferably undergo surface modification using surface modifying agents containing carboxylic acid functional groups, isocyanate functional groups or epoxy functional groups. Likewise, a contact lens having surface carboxylic acid groups preferably undergo surface modification using surface modifying agents containing glycidyl methacrylate (GMA) monomer units to provide epoxy functional groups. The reaction of the contact lens containing surface reactive functional groups and the reactive surface modifying agent is conducted under conditions known to those of skill in the art.

In the case where reactive groups are not present in the substrate material, they can be added. For example, by using a surface activation treatment such as oxygen plasma, ammonia-butadiene-ammonia (ABA) treatments and hydrogen-ammonia-butadiene-ammonia (HABA) treatments. Plasma treatment of substrate materials is known and is described in U.S. Pat. No. 6,193,369 Valint et al., U.S. Pat. No. 6,213,604 Valint et al. and U.S. Pat. No. 6,550,915 Grobe, III.

Methods of coating the substrate would include dip coating of the substrate into a solution containing the surface modifying agent. The solution containing the surface modifying agent may contain substantially the surface modifying agent in solvent or may contain other materials such as cleaning and extracting materials. Other methods could include spray coating the device with the surface modifying agent. In order for the covalent bonding reaction to occur, it may be necessary to use suitable catalysts, for example, condensation catalyst. Alternatively, the substrate and the other surface modifying agent may be subjected to autoclave conditions. In certain embodiments, the substrate and the surface modifying agent may be autoclaved in the packaging material that will contain the coated substrate. Once the reaction between the substrate and the surface modifying agent has occurred, the remaining surface modifying agent could be substantially removed and packaging solution would be added to the substrate packaging material. Sealing and other processing steps would then proceed as they usually do. Alternatively, the surface modifying agent could be retained in the substrate packaging material during storage and shipping of the substrate device to the end user.

A general method of coating is now described. Medical devices, such as commercial SofLens59™ contact lenses, are removed from the packaging and soaked in purified water for at least 15 minutes prior to being placed in polymer solution. It should be recognized by persons skilled in the art that the quantities of a solution disclosed herein may be adjusted under specific circumstances to accommodate the size of the medical device. Glass vials are labeled and filled with about 4 ml of a polymer solution, and a lens is placed in each vial. When two polymer solutions are used for coating, they are mixed together immediately prior to placing in the vials. The vials are capped with silicone stoppers and crimped aluminum caps, then placed in an autoclave for one 30-minute cycle. The treated lenses are allowed to cool for a minimum of 3 hours, then removed from the vials and rinsed at least three times with deionized water. The rinsed lenses are then placed into new vials containing 4 ml of borate buffered saline (phosphate for samples undergoing bacterial adhesion testing) and autoclaved for one 30-minute cycle for sterilization.

Other types of contact lenses, such as those comprising other hydrogel materials can be treated with coating polymers, as disclosed above. In one embodiment, PureVision™ contact lenses comprising Balafilcon A hydrogel material, disclosed in U.S. Pat. No. 5,260,000, which is incorporated herein by reference, a surface-treated with a coating polymer as disclosed above. (PureVision™ contact lenses are available from Bausch and Lomb Incorporated, Rochester, N.Y.) In one aspect, PureVision™ contact lenses were first treated with a plasma discharge generated in a chamber containing air and ammonia to increase the population of reactive surface functional groups. A solution for surface treatment comprised segmented block poly(DMA-co-GMA) and poly(acrylic acid).

The silicone hydrogel contact lenses are packaged in a container that includes a receptacle portion to hold the contact lens and a sterile packaging solution. Examples of the container are conventional contact lens blister packages. This receptacle, containing the contact lens immersed in the solution, is hermetically sealed, for example, by sealing lidstock on the package over the receptacle. For example, the lidstock is sealed around a perimeter of the receptacle.

The solution and the contact lens are sterilized while sealed in the package receptacle. Examples of sterilization techniques include subjecting the solution and the contact lens to thermal energy, microwave radiation, gamma radiation or ultraviolet radiation. A specific example involves heating the solution and the contact lens, while sealed in the package container, to a temperature of at least 100° C., more preferably at least 120° C., such as by autoclaving.

The packaging solution is an aqueous solution that includes the interactive segmented block copolymer, preferably in an amount of 0.02 to 5.0 weight percent, based on total weight of the packaging solution. The specific amount of interactive segmented block copolymer will vary depending on the substrate and the copolymer, but generally, the interactive segmented block copolymer will be present in an amount within this range.

The packaging solutions preferably have a pH of about 6.0 to 8.0, more preferably about 6.5 to 7.8, and most preferably 6.7 to 7.7. Suitable buffers include monoethanolamine, diethanolamine, triethanolamine, tromethamine(tris(hydroxymethyl)aminomethane, Tris), Bis-Tris, Bis-Tris Propane, borate, citrate, phosphate, bicarbonate, amino acids, and mixtures thereof. Examples of specific buffering agents include boric acid, sodium borate, potassium citrate, citric acid, Bis-Tris, Bis-Tris Propane, and sodium bicarbonate. When present, buffers will generally be used in amounts ranging from about 0.05 to 2.5 percent by weight, and preferably from 0.1 to 1.5 percent by weight. Some of the interactive surface active segmented block copolymers will act as buffers, and if desired, a supplemental buffering agent may be employed. It has been found that stabilization is dependent on pH, as illustrated in the accompanying examples.

The packaging solutions may further include a tonicity adjusting agent, optionally in the form of a buffering agent, for providing an isotonic or near-isotonic solution having an osmolality of about 200 to 400 mOsm/kg, more preferably about 250 to 350 mOsm/kg. Examples of suitable tonicity adjusting agents include sodium and potassium chloride, dextrose, glycerin, calcium and magnesium chloride. When present, these agents will generally be used in amounts ranging from about 0.01 to 2.5 weight percent and preferably from about 0.2 to about 1.5 weight percent.

Optionally, the packaging solutions may include an antimicrobial agent, but it is preferred that the solutions lack such an agent.

The reactive segmented block copolymers useful in certain embodiments of the present invention may be prepared according to syntheses well known in the art and according to the methods disclosed in the following examples. Surface modification of contact lenses using one or more surface modifying agents in accordance with the present invention is described in still greater detail in the examples that follow.

EXAMPLES Example A Synthesis of NVP-b-GVC Copolymer

AIBN (46 mgs; 2.82×10⁻⁴ mol) was added to a 100 mL Schlenk flask equipped with a magnetic stirring bar. To the flask was added 586 mgs (2.82×10⁻⁴) of ethyl-α-(O-ethylxanthyl)propionate (EEXP) dissolved in a small amount of dioxane. Dioxane (15 ml) and N-vinylpyrrolidone (NVP) [15 ml; 0.141 mol] were added to the Schienk flask, which was then sealed and purged with N₂ for 30 minutes. The flask was placed in an oil bath (60° C.) for 23 hours. After cooling to RT, 20 ml of THF was added to the flask and the reaction was precipitated into diethyl ether. The precipitate was isolated by filtration and dried in vacuo yielding 10.53 grams of white solid (PVP MacroRAFT agent).

The second binding block (GVC) was added to the PVP MacroRAFr agent in a second reaction. Two grams of PVP MacroRAFT agent (approx. 4.0×10⁻⁴ mol based on assumption of 5K mol wt) was added to a 100 mL Schlenk flask along with 4 mL of 1,4-dioxane and a stir bar. 1.136-g (2.82×10⁻⁴ mol) of Glycidyl vinyl carbamate (N-vinyl) and 20 mgs of AIBN (1.22×10⁻⁴ mol) were then added to the flask which was sealed and purged with N2 for 30 minutes. The viscous mixture was placed in an oil bath (6° C.) for 22½ hours. The reaction was cooled to RT and 5 ml of THF was added to the flask before the product was precipitated into diethyl ether. The precipitate was filtered and dried in vacuo at 25° C. to yield 2.44 grams of isolated product. *Note: Glycidyl vinyl carbamate is the product from the reaction of glycidol with vinyl isocyanate.

Both the PVP MacroRAFT agent and the block copolymer of NVP and GVC were characterized by proton NMR (CDCl₃) and GPC and the data support the incorporation of a GVC block onto the end of the PVP chain. The GPC shows a shift in the elution peak to shorter times (higher MW) after the addition of the GVC block. In addition, the NMR spectra shows peaks for the glycidyl groups present at 2.65 ppm and 2.85 ppm that are not present in the spectra of the PVP MacroRAFT agent. The integration in the NMR spectrum shows that there is a mole ratio of PVP:PGVC of approximately 7:1.

Example B Synthesis of DMA-b-GMA Copolymer

Weighed 353 mgs (0.97 mmol) of S-1-Dodecyl-S-(α, α′-dimethyl-α″-acetic acid)trithiocarbonate and 33 mgs of AIBN into a 50 ml Schlenk flask. Added 10 ml (97 mmol) of N,N-Dimethylacrylamide (DMA) and 20 ml of tetrahydrofuran (THF) to the flask, sealed flask with a septum and then purged with argon to deoxygenate for 30 mins. Placed flask in a 50° C. oil bath for 4.5 hrs. In a separate container, 2.0 ml (14.66 mmol) of glycidyl methacrylate (GMA) was bubbled with argon for 30 mins., then added to the flask after 4.5 hrs. *Note: A small aliquot was taken from the flask immediately before GMA addition and precipitated into diethyl ether. The reaction was stopped 15 hours after GMA addition (19.5 hrs total reaction time). The final product was dissolved in THF and precipitated into diethyl ether.

Both the first precipitate and the block copolymer of DMA and GMA were characterized by proton NMR (CDCl3) and GPC. The GPC shows a shift in the elution peak to shorter times (higher MW) after the addition of the GMA block. In addition, the NMR spectra of the block copolymer shows peaks for the glycidyl methacrylate contributions at 3.7 ppm and 4.3 ppm.

*Note: This polymerization yields a block copolymer, PDMA-block-(PGMA-co-PDMA), in which the second block is actually a statistical copolymerization of the GMA and any remaining DMA that had not been polymerized at the time of the GMA addition. The second “block”, is therefore compositionally heterogeneous. However, given the reactivity ratios of this pair of monomers (rDMA˜0.5, rGMA˜2.5, assuming GMA and MMA behave similarly) the GMA should be preferentially incorporated into the second “block”. A polymerization that yields a statistical copolymerization or compositionally heterogeneous block as the second block would also be considered to be a reactive segmented block copolymer according to the invention herein.

Additionally, the amount of remaining DMA monomer can be monitored by GC and the addition of the second monomer can occur after all the DMA in the reaction is consumed.

Example C Removal of End Group

To remove the RAFT end group, 4.0 grams of the copolymer from example B (DMA-b-GMA) was dissolved in 15 mL of dioxane in a round bottom flask. To the flask was added 250 microliters of tris(trimethylsilyl)silane and 65.8 mgs of AIBN. The solution was sparged with nitrogen for 30 minutes and then heated at 80 ° C. for 12 h under a nitrogen blanket. The cooled solution was precipitated by dropwise addition into diethyl ether. The white solid was collected by vacuum filtration and vacuum dried at RT. Cleavage of the trithiocarbonate end group was evidenced by the loss of yellow color of the product and the disappearance of the dodecyl resonances in the proton NMR.

Example D Synthesis of a Matrix of GMA-b-DMA Copolymers Where the MW of Each of the Blocks is Varied

TABLE 2 MW DMA MW GMA DMA DMA CTR CTR GMA GMA block block Reaction (mL) (mol) (mgs) (mol) (mL) (mol) (theoretical) (theoretical) 2673-208 20 0.194 700 0.00194 4.0 0.0293 9,900 2,140 2748-114 20 0.194 350 0.00097 2.0 0.0146 19,800 2,140 2748-115 20 0.194 350 0.00097 4.0 0.0293 19,800 4,275 2748-116 20 0.194 350 0.00097 8.0 0.0586 19,800 8,550 2748-117 20 0.194 700 0.00194 2.0 0.0146 9,900 1,070 2748-118 20 0.194 700 0.00194 4.0 0.0293 9,900 2,140 2748-119 20 0.194 700 0.00194 8.0 0.0586 9,900 4,275 2748-120 10 0.097 700 0.00194 2.0 0.0146 4,950 1,070 2748-121 10 0.097 700 0.00194 4.0 0.0293 4,950 2,140 2748-122 10 0.097 700 0.00194 8.0 0.0586 4,950 4,275 *~33 mgs of AIBN were added to all of the reactions *Note: All reactions were carried out in a similar fashion using the amounts shown in the table above. Reaction 2748-114 is described below as an example of the procedure used. Weighed 350 mgs (0.97 mmol) of S-1-Dodecyl-S-(α,α′-dimethyl-α″-acetic acid)trithiocarbonate and 33 mgs of AIBN into a 250 ml round bottom flask. Added 20 ml (194 mmol) of N,N-Dimethylacrylamide (DMA) and 60 ml of dioxane to the flask, sealed flask with a septum and then purged with argon to deoxygenate for 30 mins. Placed flask in an oil bath (50° C.) for 6.0 hrs. In a separate container, 2.0 ml (14.66 mmol) of glycidyl methacrylate (GMA) was bubbled with argon for 30 mins., then added to the flask after 6.0 hrs. *Note: A small aliquot was taken from the flask immediately before GMA addition and precipitated into diethyl ether. The reaction was stopped 15 hours after GMA addition (19.5 hrs total reaction time). The final product was precipitated out of the reaction mixture into diethyl ether.

Both the first precipitate and the block copolymer of DMA and GMA were characterized by proton NMR (CDCl3) and GPC. The GPC shows a shift in the elution peak to shorter times (higher MW) after the addition of the GMA block. In addition, the NMR spectra of the block copolymer shows peaks for the glycidol methacrylate contributions at 3.7 ppm and 4.3 ppm. GPC data for these polymers using DMF as an eluent are shown below, using both PMMA standards and PVP standards as calibrants. Although the trends in MW are the same, PMMA standards show MW's much closer to the theoretically expected value for polyDMA.

TABLE 3 PMMA Standards PVP Standards Sample Mw Mn Mw Mn 2748-114 20,270 15,320 432,500 207,100 2748-115 — — 534,200 219,500 2748-116 — — 681,500 282,000 2748-117 8,950 6,430 147,800 71,700 2748-118 — — 182,400 74,100 2748-119 — — 245,900 72,300 2748-120 4,000 2,540 48,600 16,100 2748-121 — — 70,100 15,000 2748-122 — — 145,100 20,0

Example E Synthesis of a Random Copolymers of DMA-r-GMA as Comparative Examples Using Conventional Free-radical Polymerization

TABLE 4 DMA DMA GMA GMA AIBN Sample (mL) (mol) (mL) (mol) (mgs) Mw Mn 2748-123A 20 0.194 2.94 0.0215 46 122,900 25,200 2748-123B 20 0.194 4.68 0.0342 50 129,800 33,000 *Note: GPC data is reported versus PMMA standards with DMF as the eluent

Both of the reactions were carried out in a similar fashion using the amounts shown in the table above. Reaction 2748-123A is described below as an example of the procedure used. Added 20 ml of DMA and 2.94 ml of GMA to a 0.5 L round bottom flask. Added 46 mgs of AIBN and 200 ml of dioxane before bubbling argon through the reaction mixture for 1 hour to remove any dissolved oxygen. Round bottom flask was then lowered into an oil bath set at 64° C. and the polymerization was allowed to proceed for 48 hours. The flask was then removed from the oil bath and the product was precipitated by dropwise addition into diethyl ether. The precipitated polymer was isolated by filtration and dried at RT in a vacuum oven.

The random copolymers of DMA and GMA were characterized by proton NMR (CDCl3) and GPC. The GPC data with DMF as an eluent are shown in the table above and the MW of both of these samples was considerably larger than their RAFT polymerized counterparts detailed in example D. In addition, the NMR spectra of the random copolymers showed peaks for the glycidol methacrylate contributions at 3.7 ppm and 4.3 ppm.

The molar ratios of DMA to GMA in the randomly polymerized samples were chosen to approximate the molar ratios of those produced by RAFT polymerization in example D. For the random samples the two polymers were DMA(90)-r-GMA(10) [2748-123A] and DMA(85)-r-GMA(15) [2748-123B]. *Mole percent of each monomer given in parenthesis.

Example F Coating of a Silicone Hydrogel Formulation

Contact lenses of a cationic silicone hydrogel formulation were prepared comprising the two silicone containing monomers shown below (M2D39+ and MI-MCR-C12); N-vinyl-2-pyrrolidone (“NVP”); tris(trimethylsiloxy)silylpropyl methacrylate (“TRIS”); 2-hydroxyethyl methacrylate (“HEMA”), a UV blocking monomer (SA monomer); and AIBN. The “reactive handle” present in this substrate was the —OH group of HEMA which was present at 18.6 parts in the formulation. The lens formulation was thermally cured between two polypropylene molds at 110° C. for 4 hours, removed from the mold and extracted in IPA for 4 hours before transferring to deionized water.

Sample 2748-118 from example D; and samples 2748-123A and 2748-123B from example E were used to prepare coating solutions. In a typical coating experiment, the lenses prepared above were placed in a polypropylene (PP) blister containing 3.8-mL of a 250 ppm (w/v) solution of subject polymer dissolved in pH=7.2 Trizma buffer. A control lot with no coating polymer was also produced. The lens blisters were sealed and autoclaved at 121° C. for 30-min. After the autoclave, the lenses were removed from the blister packages and rinsed for 24 hours in purified water and the surface was analyzed using X-ray photoelectron spectroscopy (XPS) to determine the elemental composition of the surface and static contact angle. The surface data is shown in the table below.

TABLE 5 Contact XPS Data Angle Sample C1s N1s O1s Si2p Static Control 66.5 (0.5) 4.0 (0.6) 21.1 (1.0) 8.3 (0.6) 117.3 (0.6) 2748-118 68.9 (1.1) 6.9 (0.6) 20.3 (0.6) 2.9 (1.2) 86.6 (11.0) (block) 2748- 66.0 (0.7) 3.9 (0.4) 21.5 (0.5) 8.5 (0.4) 115.4 (1.6) 123A (random) 2748- 67.0 (0.9) 5.4 (0.8) 20.9 (0.7) 6.5 (0.8) 111.3 (5.9) 123B (random)

As can be seen from the XPS data, the reactive segmented block copolymer 2748-118 leads to the largest reduction in silicon (Si2p) at the surface of the lens and the largest increase in nitrogen (N1s). This is indicative of this GMA-b-DMA reactive segmented block copolymer being efficient at reacting with the lens surface and coating the lens substrate. In addition the static contact angle for the block copolymer 2748-118 is lower than the control and either of the random copolymers, which also suggest that there is more of the hydrophilic reactive segmented block copolymer bound to the lens.

XPS data was collected on a Physical Electronics Quantera SXM (Scanning X-ray Microprobe) Sample acquisitions are rastered over a 1400 micron×100 micron analysis spot. Dual beam neutralization (ions and electrons) was used during all analysis. The instrument base pressure was 5×10⁻¹⁰ torr and during operation the pressure was less than or equal to 1×10⁻⁷ torr. Each specimen was analyzed utilizing a low-resolution survey spectra (0-1100 eV) to identify the elements present on the sample surface. Quantification of elemental compositions was completed by integration of the photoelectron peak areas. Analyzer transmission, photoelectron cross-sections and source angle correction were taken into consideration in order to give accurate atomic concentration values.

Three lenses from each lot were placed in glass vials containing HPLC grade water, and were placed on a shaker for 24 hours to rinse away unbound coating polymer. After that time the samples were placed in sterile Petri dishes and rinsed in HPLC grade water for 15 minutes. The lenses were then sliced into quarters using a clean sterile scalpel, clean tweezers and silicon free latex gloves. The quarters for XPS analysis were mounted on clean metal platens, with three posterior and three anterior sides facing up, using clean metal masks. The samples were placed in a nitrogen dry box overnight before introduction into the spectrometer.

For contact angle analysis, samples were mounted on a clean glass slide and dried overnight in a nitrogen dry box. Contact angles were measured on the dehydrated lenses at two points on each sample. The instrument used for measurement was an AST Products Video Contact Angle System (VCA) 2500XE. This instrument utilizes a low-power microscope that produces a sharply defined image of the water drop, which is captured immediately on the computer screen. HPLC water was drawn into the VCA system microsyringe, and a 0.6 μl drop is dispensed from the syringe onto the sample. The contact angle is calculated by placing three to five markers along the circumference of the drop. The software calculates a curve representing the circumference of the drop and the contact angle is recorded. Both a right and left contact angle are reported for each measurement. Reported in the table above is the average of both.

Example G Synthesis of DMA-b-GMA Copolymer with a Difunctional Trithiocarbonate

Weigh 353 mg of S,S′-bis(α,α′-dimethyl-α″-acetic acid)trithiocarbonate and 33 mg of AIBN into a 50 ml Schlenk flask. Add 10 ml of N,N-Dimethylacrylamide (DMA) and 20 ml of tetrahydrofuran (THF) to the flask. Seal flask with a septum and purge with argon to deoxygenate for 30 mins. Place flask in a 50° C. oil bath for 4.5 hrs. In a separate container, 2.0 ml of glycidyl methacrylate (GMA) is bubbled with argon for 30 mins., then added to the flask after 4.5 hrs. Stop reaction 15 hours after GMA addition and precipitate final product into diethyl ether.

Example H Coatings on a Number of Lens Substrates in Various Buffers

The example below is intended to show that a variety of substrates can be treated with the polymers set forth in this invention. The three lens materials used in this example are the silicone hydrogel detailed in example F, which will be designated RD-1881 for the purposes of this example, and the commercially available lens materials polymacon (SofLens 38®) and balafilcon A (Pure Vision®). The silicone hydrogel and polymacon contains an —OH group in the substrate as a reactive handle for the polymers used in this invention and balafilcon contains —COOH groups in the substrate.

In a typical coating experiment, the lenses stated in the table below were packaged in polypropylene (PP) blister containing 3.8-mL of between 250 ppm and 2000 ppm (w/v) solution of subject polymer dissolved in pH=7.2 BBS or TRIZMA buffer. A control lot with no coating polymer was also produced. The lens blisters were sealed and autoclaved at 121° C. for 30-min. After the autoclave, the lenses were removed from the blister packages and rinsed for 24 hours in purified water and the surface was analyzed using X-ray photoelectron spectroscopy (XPS) to determine the elemental composition of the surface. The XPS data is shown in the table below.

TABLE 6 XPS Data Sample Buffer C1s N1s O1s Si2p A) RD-1881 (control) BBS 65.2 (0.9) 4.2 (0.4) 21.8 (0.5) 8.8 (0.7) B) RD-1881 (2673-208) BBS 66.8 (1.1) 6.8 (0.4) 21.2 (0.6) 5.2 (0.9) C) RD-1881 (2673-208) TRIZMA 71.1 (2.8) 7.5 (3.7) 20.1 (0.6) 0.2 (0.4) D) RD-1881 (2673-208) MOPS 70.0 (0.4) 9.0 (0.2) 20.3 (0.3) 0.1 (0.1) E) Polymacon (control) BBS 69.0 (0.5) 0.3 (0.3) 30.7 (0.7) — F) Polymacon (2673-208) BBS 71.8 (0.7) 5.9 (0.2) 22.1 (0.6) — G) RD-1881 (2673-208) BBS 68.4 (1.4) 8.4 (0.6) 20.4 (0.7) 2.8 (1.3) H) RD-1881 (2673-208) TRIZMA 70.1 (0.3) 9.3 (0.2) 19.5 (0.2) 0.1 (0.1) I) RD-1881 (2673-208) TRIZMA 70.0 (0.2) 9.0 (0.4) 19.2 (0.3) 0.9 (0.4) J) Polymacon (Control) BBS 68.1 (1.0) — 31.9 (1.0) K) Polymacon (Example A) BBS 69.3 (1.0) 3.5 (0.7) 26.6 (1.2) — L) Balafilcon A (control) TRIZMA 64.5 (0.3) 6.4 (0.3) 19.5 (0.2) 9.6 (0.2) M) Balafilcon A (2673-208) TRIZMA 68.6 (0.4) 8.6 (0.4) 19.0 (0.3) 3.1 (0.7) Samples B, C, D, and F in the table above contain 1000 ppm of 2673-208 from example D dissolved in buffer. Sample G contains 2000 ppm of 2673-208 dissolved in pH 7.2 BBS. Sample H contains 500 ppm of 2673-208 dissolved in pH 7.2 TRIZMA buffer. Sample I and M contain 250 ppm of 2673-208 dissolved in pH 7.2 TRIZMA buffer. Sample K contains 1000 ppm of polymer made in example A

As can be seen from the XPS data, the reactive segmented block copolymer 2673-208 can be utilized to coat a variety of substrates. In samples A through D, RD-1881 lenses are treated with a solution containing 1000 ppm of DMA-b-GMA copolymer (2673-208) in different buffers. All the buffers show that there is an increase in nitrogen and a decrease in silicone concentration at the lens surface when treated with the copolymer, however the largest reduction in silicone occurs when either TRIZMA or MOPS buffer is used with the epoxide containing polymers. These buffers are preferred for enhanced reaction of these polymers. Samples E and F demonstrate that polymacon can be treated with these reactive segmented block copolymers which is shown by an increase in nitrogen and decrease in oxygen at the surface of the treated lens. This is consistent with the polyDMA containing copolymer being bound at the surface of the lens. Samples G, H, and I are part of a concentration study of the copolymer in the buffered solution and show that you can go to fairly low concentrations (250 ppm) and still obtain a significant reduction in surface silicone with these copolymers. Samples J and K are polymacon lenses which shows that lenses treated with PVP-b-GVC copolymer (Example A) show an increase in nitrogen and a decrease in oxygen, which is again consistent with the polyPVP containing copolymer being bound at the lens surface. Finally, in examples L and M, non-plasma treated balafilcon A lenses are treated with a GMA-b-DMA copolymer (2673-208) and show a substantial reduction in silicone and in increase in carbon and nitrogen indicating polymer binding.

XPS Analysis and sample preparation was identical to that detailed in example F.

While there is shown and described herein certain specific structures and compositions of the present invention, it will be manifest to those skilled in the art that various modifications may be made without departing from the spirit and scope of the underlying inventive concept and that the same is not limited to particular structures herein shown and described except insofar as indicated by the scope of the appended claims. 

1. A method of forming a surface modified medical device, the method comprising: providing a medical device having at least one group providing reactive functionality on at least one surface of the medical device; providing a surface modifying agent comprising a reactive segmented block copolymer comprising a hydrophilic block and a chemical binding unit block having reactivity that is complimentary to the at least one group providing surface functionality of the medical device; contacting the at least one surface having reactive functionality of the medical device with the surface modifying agent, and; subjecting the device surface and surface modifying agent to reaction conditions suitable for forming a covalent bond between the device surface and the surface modifying agent to form a surface modified medical device, wherein the reactive segmented block copolymer is selected from the following formulae (I)-(III): R1−[(A)m]p−[(B)n]q−X  (I) wherein R1 is a reactive residue of a moiety capable of acting as an initiator for atom transfer radical polymerization, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and X is a halogen capping group of an initiator for atom transfer radical polymerization or a derivatized reaction product, R1−[(A)m]p−[(B)n]q−R2  (II) wherein R1 is a radical forming residue of a reverse addition fragmentation transfer agent or free radical initiator, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and R2 is a thio carbonyl fragment of a chain transfer agent or a derivatized reaction product, and R1−[(B)n]q−[(A)m]p−R2−[(A)m]p−[(B)n]q−R1  (III) wherein R1 is a radical forming residue of a reverse addition fragmentation transfer agent or free radical initiator, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and R2 is a thio carbonyl thio group.
 2. The method of claim 1 wherein the medical device is prepared from a silicon containing monomer.
 3. The method of claim 2 wherein the silicon containing monomer comprises a silicon containing monomer selected from the group consisting of silicon containing vinyl carbonates, silicon containing vinyl carbamates, polyurethane-polysiloxanes having one or more hard-soft-hard blocks and end-capped with a hydrophilic monomer, fumarate containing silicon containing monomers, poly(organosiloxanes) capped with an unsaturated group at two or more ends of the molecule, polyurethane-polysiloxane macromonomers and mixtures thereof.
 4. The method of claim 2 wherein the medical device comprises as a bulk monomer mixture to be copolymerized 5 to 50 percent by weight of one or more silicon containing macromonomers, 5 to 75 percent by weight of one or more polysiloxanylalkyl(meth)acrylic monomers, and 10 to 50 percent by weight of a hydrophilic monomer.
 5. The method of claim 2 wherein the medical device comprises as a bulk monomer mixture to be copolymerized 10 to 25 percent by weight of one or more silicon containing macromonomers, 30 to 60 percent by weight of one or more polysiloxanylalkyl (meth)acrylic monomers, and 20 to 40 percent by weight of a hydrophilic monomer.
 6. The method of claim 1 wherein the medical device comprises hydrogel materials.
 7. The method of claim 1 wherein the medical device comprises silicon containing hydrogel materials.
 8. The method of claim 1 wherein the medical device comprises vinyl functionalized polydimethylsiloxanes copolymerized with hydrophilic monomers.
 9. The method of claim 1 wherein the medical device comprises fluorinated monomers.
 10. The method of claim 1 wherein the medical device comprises methacrylate functionalized fluorinated polyethylene oxides copolymerized with hydrophilic monomers.
 11. The method of claim 1 wherein the medical device is selected from the group consisting of heart valves, intraocular lenses, intraocular lens inserters, contact lenses, intrauterine devices, vessel substitutes, artificial ureters, vascular stents, phakic intraocular lenses, aphakic intraocular lenses, corneal implants, catheters, implants, and artificial breast tissue.
 12. The method of claim 11 wherein the medical device formed is a soft contact lens.
 13. The method of claim 12 wherein the medical device is a silicon containing hydrogel contact lens material.
 14. The method of claim 1 wherein the medical device has at least one surface functionality selected from the group consisting of epoxides, carboxylic acids, anhydrides, oxazolinones, lactams, lactones, amines, hydroxys, hydrazines, hydrazides, thiols, nucleophilic groups, electrophilic groups, carboxylic esters, imide esters, orthoesters, carbonates, isocyanates, isothiocyanates, aldehydes, ketones, thiones, alkenyls, acrylates, methacrylates, acrylamides, sulfones, maleimides, disulfides, iodos, sulfonates, thiosulfonates, silanes, alkoxysilanes, halosilanes, phosphoramidate and alcohol functionality.
 15. The method of claim 14 wherein the surface functionality is selected from the group consisting of aldehyde hydrates, hemiacetals, acetals, ketone hydrates, hemiketals, ketals, thioketals, and thioacetals.
 16. The method of claim 14 wherein the surface functionality is selected from the group consisting of succinimidyl carbonate, succinimidyl ester, maleimide, benzotriazole carbonate, glycidyl ether, imidazoyl ester, p-nitrophenyl carbonate, acrylate, tresylate, aldehyde, and orthopyridyl disulfide.
 17. The method of claim 1, wherein the reactive segmented block copolymer has a chemical binding unit selected from the group consisting of monomers comprising a functionality selected from the group consisting of epoxides, carboxylic acids, anhydrides, oxazolinones, lactams, lactones, amines, hydroxys, hydrazines, hydrazides, thiols, nucleophilic groups, electrophilic groups, carboxylic esters, imide esters, orthoesters, carbonates, isocyanates, isothiocyanates, aldehydes, ketones, thiones, alkenyls, acrylates, methacrylates, acrylamides, sulfones, maleimides, disulfides, iodos, sulfonates, thiosulfonates, silanes, alkoxysilanes, halosilanes, phosphoramidate and alcohol functionality.
 18. The method of claim 1, wherein the reactive segmented block copolymer has a hydrophilic unit monomer selected from the group consisting of 2-hydroxyethyl methacrylate, glycerol methacrylate, methacrylic acid, acrylic acid, methacrylamide, acrylamide, N,N′-dimethylmethacrylamide, N,N′-dimethylacrylamide; ethylenically unsaturated poly(alkylene oxide)s, cyclic lactams, N-vinyl-2-pyrrolidone, hydrophilic vinyl carbonate, hydrophilic vinyl carbamate monomers, 2-hydroxyethyl acrylate, 2-(2-ethoxyethoxy)ethyl (meth)acrylate, glyceryl (meth)acrylate, poly(ethylene glycol (meth)acrylate), tetrahydrofurfuryl (meth)acrylate, N-vinyl acetamide, copolymers, derivatives and combinations thereof.
 19. The method of claim 1, wherein the reactive segmented block copolymer has a chemical binding unit comprises between 1 and about 1,000 units.
 20. The method of claim 1, wherein the reactive segmented block copolymer has a chemical binding unit comprises between 1 and about 100 units.
 21. The method of claim 1, wherein the reactive segmented block copolymer has a chemical binding unit comprising between 1 and about 30 units.
 22. The method of claim 1, wherein the reactive segmented block copolymer has a hydrophilic block comprising between 1 and about 10,000 units.
 23. The method of claim 1, wherein the reactive segmented block copolymer has a hydrophilic block comprising between about 10 and about 1,000 units.
 24. The method of claim 1, wherein the reactive segmented block copolymer has a hydrophilic block comprising between about 20 and about 300 units.
 25. The method of claim 1 wherein the step of subjecting the device surface and surface modifying agent to reaction conditions suitable for forming a covalent bond between the device surface and the surface modifying agent to form a surface modified medical device occurs under autoclave conditions.
 26. The method of claim 25 further comprising the step of applying a lid stock to a package containing the device and the surface modifying agent prior to subjecting the medical device to a step of autoclaving.
 27. The method of claim 25 further comprising the steps of removing the surface modifying agent after autoclaving, rinsing the coated device, providing a storage solution and further autoclaving the device to sterilize the device.
 28. The method of claim 1 wherein one of the chemical binding unit block or the hydrophilic block is a statistical copolymerization or compositionally heterogeneous block.
 29. The method of claim 1 wherein the reactive segmented block copolymer further comprises at least one block selected from the group consisting of nonbinding blocks, nonhydrophilic blocks and combinations thereof.
 30. A surface modified medical device comprising: a medical device having at least one group providing reactive functionality on at least one surface of the medical device; and a reactive segmented block copolymer comprising a chemical binding unit block and a hydrophilic block applied to the surface of the medical device; whereby a chemical reaction between the surface functionality of the medical device and the one or more reactive segmented block copolymer comprising a chemical binding unit block and a hydrophilic block forms covalent bonds there between, wherein the reactive segmented block copolymer is selected from the following formulae (I)-(III): R1−[(A)m]p−[(B)n]q−X  (I) wherein R1 is a reactive residue of a moiety capable of acting as an initiator for atom transfer radical polymerization, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and X is a halogen capping group of an initiator for atom transfer radical polymerization or a derivatized reaction product, R1−[(A)m]p−[(B)n]q−R2  (II) wherein R1 is a radical forming residue of a reverse addition fragmentation transfer agent or free radical initiator, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and R2 is a thio carbonyl fragment of the chain transfer agent or a derivatized reaction product, and R1−[(B)n]q−[(A)m]p−R2−[(A)m]p−[(B)n]q−R1  (III) wherein R1 is a radical forming residue of a reverse addition fragmentation transfer agent or free radical initiator, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and R2 is a thio carbonyl thio group.
 31. The surface modified medical device of claim 30 wherein the medical device is selected from the group consisting of heart valves, intraocular lenses, intraocular lens inserters, contact lenses, intrauterine devices, vessel substitutes, artificial ureters, vascular stents, phakic intraocular lenses, aphakic intraocular lenses, corneal implants, catheters, implants, and artificial breast tissue.
 32. The surface modified medical device of claim 31 wherein the medical device is a hydrophilic contact lens.
 33. The surface modified medical device of claim 31 wherein the medical device is a hydrogel contact lens. 